Engineered Mosquitoes Cannot Be Infected With or Transmit Any Dengue Virus

A swarm of mosquitoes hover near an infected blood meal opportunity. Glowing transgenic mosquitoes have a protective DNA barrier that prevents them from supporting blue dengue virus (DENV) particle replication. In contrast, unprotected wildtype mosquitoes are able to become infected and transmit DENV. A unique antibody-expressing transgene has the ability to provide resistance against four different DENV serotypes. Courtesy of Buchman A, et al. (2020)

Genetically engineered mosquitoes are resistant to multiple types of dengue virus (DENV), according to a study published Jan. 16 in the open-access journal PLOS Pathogens by Prasad Paradkar of the Australian Animal Health Laboratory, and Omar Akbari of the University of California, San Diego, and colleagues. As noted by the authors, this is the first engineered approach that targets all types of DENV, which is crucial for effective disease suppression.

Dengue is a mosquito-borne viral disease that represents a pressing global problem, and new solutions are needed to prevent its transmission. DENV is mainly transmitted by Aedes aegypti mosquitoes. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. In the new study, the authors describe the development of A. aegypti mosquitoes synthetically engineered to be resistant to multiple types of DENV.

These mosquitoes express a gene encoding an engineered single-chain variable fragment (scFv) derived from a broadly neutralizing DENV human monoclonal antibody. Mosquitoes expressing the anti-DENV scFv cannot be infected with or transmit any of the four types of DENV, so they should not be able to transmit the virus to humans. Taken together, these results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail related viruses. According to the authors, this strategy could be coupled with a gene-drive system to rapidly convert wild mosquito populations into genetically modified mosquitoes that would be completely resistant to DENV transmission.

Akbari adds, “The most important aspect of this study is the fact that we engineered mosquitoes to be refractory to all major serotypes of Dengue virus. This may serve as a genetic tool to control Dengue in the wild in the future.

Reference: Buchman A, Gamez S, Li M, Antoshechkin I, Li H-H, Wang H-W, et al. (2020) Broad dengue neutralization in mosquitoes expressing an engineered antibody. PLoS Pathog 16(1): e1008103.

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